The overall goal of this proposal is to develop a novel approach for the treatment of alcohol abuse and dependency using unique and patented biodegradable gel formulations for controlled release of nalmefene. These novel biodegradable gel formulations will be able to maintain therapeutic concentrations of nalmefene for a prolonged period of time, following a single subcutaneous injection, thereby creating a product that will significantly improve patient compliance. Therefore, the specific aims of this study are as follows: (1) Develop and Evaluate In Vitro Drug Release Rates from Novel Injectable Gels Loaded with Nalmefene. The first step in this study will be to characterize critical factors affecting in vitro release rates of nalmefene. (2) Ascertain the How Long Therapeutic Plasma Concentrations of Nalmefene can be Maintained In Vivo after a Single Subcutaneous Injection. The duration of therapeutic plasma concentration of nalmefene released from two optimized drug-loaded gel formulations will be examined in rats following a single subcutaneous injection of the gels. The underlying hypothesis of our research is that the novel injectable biodegradable gel loaded with nalmefene will overcome the major disadvantages of the present oral therapy with naltrexone, i.e., significant first pass metabolism and poor patient compliance. PROPOSED COMMERCIAL APPLICATION: A United States patent application for this novel biodegradable drug delivery system has been granted and has also been filed in other countries. A controlled release drug delivery system of nalmefene, which is biodegradable and can maintain therapeutic concentrations of the drug for approximately 2-4 weeks following a single injection in alccoholic dependent patients, will guarantee patient compliance and reduce treatment cost.